Marina Sarris

Date Published: March 14, 2023

Most scientists agree that both our genes and the environment contribute to autism, but what exactly do they mean by the environment?

Many immediately think of the outdoors ─ the air we breathe, for instance ─ as making up our environment, but when talking about autism, that is only part of the story.

An environmental factor in autism is something, other than DNA, that affects a child before, during, or after birth.

“I like to think about the environment as things that could be modified,” says Heather E. Volk, Ph.D., M.P.H, associate professor at the Johns Hopkins Bloomberg School of Public Health and director of the Wendy Klag Center for Autism and Developmental Disabilities. Volk teaches epidemiology, the study of factors that contribute to health and medical conditions.

Researchers have pinpointed environmental factors that have the most potential for contributing to autism, probably in combination with genes.¹ They include:

• Exposure to air pollution and pesticides during pregnancy
• Medical conditions and illnesses during pregnancy, such as fever, infection, diabetes, obesity, an immune system condition, pre-eclampsia (a high blood pressure disorder), or taking the anti-epilepsy drug valproic acid²
• Birth complications, such as being born very early or very small, or not getting enough oxygen during delivery
• Having older parents, or being born too soon, or too long, after an older sibling

Some of these factors may overlap. For example, an older mother is more likely to develop gestational diabetes, which is a type of diabetes that only happens during pregnancy. Her diabetes, in turn, might cause the baby to be very large, which could cause complications during birth.

Researchers have studied certain chemicals and pollutants because they can affect our nervous systems and a developing fetus.

Research by Volk and others has found that children exposed to higher levels of some air pollutants before and after birth were more likely to have autism.^3,4 Other research has found a similar link in the children of mothers who lived near farms that spread pesticides, or who worked around hazardous chemicals, during pregnancy.^5,6

Other possible environmental factors include exposure to flame retardants, which are chemicals added to electronics, appliances, mattresses, carpets, and other home products to decrease the risk of fire. Scientists are also studying phthalates, which are chemicals used in plastics, soaps, shampoos, and other products.

Research has not found any link between vaccines and autism.

“Environmental factors can be big and varied. But they fall into groups that travel together in terms of where, and how, we might think about intervention,” Volk says. She discusses gene-environment interactions in autism during this recorded SPARK webinar.

Researchers like Volk look for links, or statistical associations, between autism and an environmental factor. For example, is autism more likely in people exposed to air pollution from busy highways? But scientists don’t stop there. A statistical link does not prove that a pollutant causes autism, Volk explains.

So scientists ask more questions: When was the exposure to pollution, and is there a good biological reason why the pollutant might cause autism? And have multiple studies involving many different people found the same link?

Where Do Genes Fit Into the Autism Picture?

Of course, genes play a major role in autism.

For decades, studies of twins have shown the significant influence of genes on autism. Identical twins, who have the same DNA, are much more likely to both have autism than fraternal twins, who share about half of their DNA. A 2019 study of people in five countries estimated that 80 percent of autism is genetic.⁷

Researchers have identified more than 850 genes that contribute to autism when the genes have rare variations in their code. These genetic variations are often not inherited from parents. Instead, they may occur for the first time in the embryo. These variations are called “de novo,” a Latin phrase for new.

Up to 10 percent of people who contribute DNA to the SPARK autism study have a variation in an autism gene, and most of these variations are de novo. De novo variations often play a major role in autism.

But some genetic variations may have a smaller influence on autism and may not cause autism in every person who has them. In some instances, common variations in a gene, when combined with a particular exposure during pregnancy, may contribute to autism, Volk says.

MTHFR ─ An Example of How Genes and Environmental Factors May Interact in Autism

People who have a common variation of the MTHFR gene may not process folic acid, a B vitamin, as well as others. If a pregnant woman has this variation, and she does not get enough of the B vitamin (an environmental factor), her baby may be more likely to have autism, Volk says.

Some studies suggest that taking adequate folic acid around the time of a baby’s conception may counteract the effect of toxic chemicals in the environment and decrease the likelihood of autism.⁸

Folic acid is included in prenatal vitamins and added to the flour used in fortified cereal, bread, and pasta in the United States. Taking folic acid before and during pregnancy also decreases the chances of a baby being born with spina bifida, a defect of the spine.

Perhaps nutritional factors may explain why researchers have found that a child conceived less than 18 months after the birth of an older brother or sister is more likely to have autism, Volk says.

That same study of birth timing also found that children conceived more than five years after their older sibling were more likely to have autism.⁹ Maybe that is because the parents were older, which is an environmental factor that also can be genetic, Volk says. Older parents may have more changes in the DNA in the cells that combine to form the embryo.

A Shared Environment: The Experience of Twins

Alycia Halladay, Ph.D., is the parent of twin girls, one of whom has autism. A SPARK research participant, she is interested in how both genes and the environment affect autism. Like all twins, her daughters shared the same prenatal environment, at the same time. But as fraternal twins, the 12-year-olds do not have the same DNA.

Was there something about them that made one twin more likely to have autism, or one twin less likely, she wonders. “That’s why it’s so important to include both genetics and the environment in the equation, because there are so many interactions there,” says Halladay, who is chief science officer at the Autism Science Foundation.

Genetic studies, like SPARK, provide an opportunity to better understand how genes and environmental factors throughout a person’s life influence the kind of autism they have, and whether they have other medical conditions, such as epilepsy and mental health concerns, Volk says. “It’s likely that many small changes are working together.”

Knowing the factors that increase a child’s chances of having autism could lead to earlier autism screenings of those children, she says. And that could give those who have autism a head start on services.

Resources

• Watch a SPARK webinar, Exploring Gene-Environment Interactions in Autism, with Heather E. Volk, Ph.D., M.P.H.
• See SPARK articles and webinars about causes of autism.

References

1. National Institute of Environmental Health Sciences Autism. www.niehs.nih.gov. Accessed March 14, 2023
2. Wiggs K.K. et al. Neurology 95, e3232-e3240 (2020) PubMed
3. Volk H.E. et al. Environ Res. 196, 110320 (2021) PubMed
4. Flanagan E. et al. Sci. Rep. 13, 3848 Epub ahead of print (2023) PubMed
5. Windham G.C. et al. Autism Res. 6, 57-63 (2013) PubMed
6. Shelton J.F. et al. Environ. Health Perspect. 122, 1103-1109 (2014) PubMed
7. Bai D. et al. JAMA Psychiatry 76, 1035-1043 (2019) PubMed
8. Volk H.E. et al. Pediatrics 149, e2021053012 (2022) PubMed
9. Schieve L.A. et al. Autism Res. 11, 81-94 (2018) PubMed